Antibiotic-induced cell wall fragments of Staphylococcus aureus increase endothelial chemokine secretion and adhesiveness for granulocytes

Antibiotics release inflammatory fragments, such as lipoteichoic acid (LTA) and peptidoglycan (PG), from the cell wall of Staphylococcus aureus. In th is study, we exposed S. aureus cultures to a number of beta-lactam antibiot ics (imipenem, flucloxacillin, and cefamandole) and protein synthesis-inhib iting antibiotics (erythromycin, clindamycin, and gentamicin) and investiga ted whether supernatants of these cultures differ in their capacity to stim ulate endothelial cells (EC), After 24 h of incubation, endothelial adhesiv eness for leukocytes, surface expression of various adhesion molecules, and secretion of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were measured. Supernatants of beta-lactam-exposed cultur es (designated beta-lactam supernatants) enhanced the adhesiveness of EC fo r granulocytes, whereas those of protein synthesis-inhibiting antibiotic-ex posed cultures (designated protein synthesis-inhibitor supernatants) did no t. This hyperadhesiveness coincided with a higher intercellular adhesion mo lecule-1 expression on the surface of the stimulated EC, In addition, EC st imulated with beta-lactam supernatants secreted significantly higher concen trations of the chemokines IL-8 and MCP-1 than those stimulated with protei n synthesis-inhibitor supernatants, The finding that the concentrations of LTA and PG in beta-lactam supernatants were much higher than those in prote in synthesis-inhibitor supernatants suggests that the observed differences in stimulatory effect between these supernatants are a result of difference s in the release of cell wall fragments, although the presence of other sti mulatory factors in the supernatants cannot be excluded. In conclusion, our results argue for a release of LTA and PG from S, aureus after exposure to beta-lactam antibiotics that enhances the development of a systemic inflam matory response by stimulating EC such that adhesiveness for granulocytes i s increased and large amounts of IL-8 and MCP-1 are secreted.